While orthodontic tooth movement occupies a prominent position in clinical dentistry, teeth are capable of extensive movement and displacement without the use of orthodontic appliances. Examples of non- orthodontic tooth movement include tooth eruption and the movement of embryonic tooth germs within the jaws as well as distal and mesial drift of the dentition. While these types of tooth movement resemble osteoclast-mediated resorption of large volumes of bone, preliminary studies from our laboratory have suggested that neither RANKL nor inflammatory cytokines play a significant role in physiological tooth movement. We have therefore postulated the presence of at least two different pathways of osteoclast activation associated with tooth movement, a non-inflammatory pathway without significant RANKL upregulation that is associated with physiological tooth movement and an inflammatory RANKL-mediated pathway that is activated during orthodontic tooth movement. In order to further test our hypothesis, we have designed a research plan in which we will be comparing putative bone resorption systems between a physiologic tooth movement model that we have established in previous studies (Holliday et al. 2005) and an orthodontic tooth movement model that we have further refined in our laboratory (preliminary data section). These experiments will provide experimental data for the development of important clinical aids for orthodontic treatment and might greatly benefit millions of patients suffering from malocclusion.